The search for strong analgesics which also possess minimal potential for dependency has been among the highest priority efforts in pharmacological research. These research efforts have, to a great extent, involved chemical modifications of the opiate structure and the discovery of chemically novel compounds which possess morphine-like activity.
The concept of multiple opioid receptors has been supported by studies with nalorphine and a series of benzomorphans which display unusual pharmacological properties dissimilar from morphine, yet blocked by the opioid antagonists. [See, for example, W. R. Martin, et al., J. Pharmacol. Exp. Ther., 197:517-531 (1976)].
The existence of multiple types of opioid receptors is of importance because it suggests the possibility of separating the desirable analgesic and psychotherapeutic effects of a drug compound from the undesirable abuse potential or habituating effect.
U.S. Pat. No. 4,145,435 describes certain 2-amino-cycloaliphatic amide compounds as analgesic. In particular, trans-3,4-dichloro-N-methyl-N-[2-pyrrolidinyl)cyclohexyl]benzeneacetamide has been reported to possess selective kappa opioid agonist activity, and therefore to possess analgesic activity without attendant dependence liability. [See P. V. Vonvoigtlander, et al., J. Pharmacol. Exp. Ther., 224:7-12 (1983)].
Recently, the diuretic effect of various opioid agonists and antagonists has been studied, and it has been shown that kappa agonists tend to increase urination, while mu agonists decreased urination. [See J. D. Leander, J. Pharmacol. Exp. Ther., 227:35-41 (1983)]. These findings suggest that opioid agonists and antagonists also possess potential as diuretics.
U.S. Pat. No. 4,656,182 describes certain trans-1,2-diaminocyclohexyl amides useful as analgesics, diuretics, and psychotherapeutics.
U.S. Pat. No. 4,463,013 discloses certain oxygen substituted amino-cyclohexyl-benzeneacetamides as diuretics.
U.S. Pat. No. 4,438,130 discloses certain monooxa-, thiaspiro-cyclic-benzeneacetamide and benzamide compounds useful as analgesics.